Ketenimines are an important class of reactive species and useful synthetic intermediates. During the last two decades several practical and versatile approaches to ketenimines have been developed, leading to exhaustive investigations on ketenimine chemistry and the discovery of a variety of highly efficient reactions. Five types of reactions for ketenimines have been reported, including nucleophilic additions (ketenimines can be used as both electrophiles and nucleophiles), radical additions, cycloaddition reactions, electrocyclic ring closure reactions, and σ rearrangements. Furthermore, numerous complex organic compounds, particularly the biologically interesting heterocycles, have been constructed using these methodologies. The review of these accomplishments is presented here.

The thriving chemistry of ketenimines

Herein we describe a novel, hollow-structured zeolitic imidazolate framework (ZIF-8-H) nanosphere as a highly efficient catalyst for [3+3] cycloaddition reactions. The programmed installation of acidic Zn2+ species and basic imidazolate moieties creates a synergistic catalytic system. Appropriate positioning of these functionalities in the catalytic system makes it possible to bring two substrates into close proximity and activate them cooperatively. Moreover, the flexible shell and the surface mesopores of ZIF-8-H provide the capacity for favorable binding of various sized substrates, stabilizing intermediates via their multiple force networks and the increased accessibility of the active sites. These features render ZIF-8-H a more highly active promoter than its homogeneous precursors, bulk ZIF-8 and ZIF-8-N nanoparticles. Finally, the robust catalyst can be easily recovered and reused 10 times without loss of catalytic activity.

Hollow zeolitic imidazolate framework nanospheres as highly efficient cooperative catalysts for [3+3] cycloaddition reactions.

Enantioselective synthesis of dihydropyridinones via NHC-catalyzed aza-Claisen reaction.

Recent Highlights in Ketenimine Chemistry

Copper-catalyzed oxidative alkynylation of diaryl imines with terminal alkynes: a facile synthesis of ynimines.

A detailed study of amidine synthesis from N-allyl-N-sulfonyl ynamides is described here. Mechanistically, this is a fascinating reaction consisting of diverging pathways that could lead to deallylation or allyl transfer depending upon the oxidation state of palladium catalysts, the nucleophilicity of amines, and the nature of the ligands. It essentially constitutes a Pd(0)-catalyzed aza-Claisen rearrangement of N-allyl ynamides, which can also be accomplished thermally. An observation of N-to-C 1,3-sulfonyl shift was made when examining these aza-Claisen rearrangements thermally. This represents a useful approach to nitrile synthesis. While attempts to render this 1,3-sulfonyl shift stereoselective failed, we uncovered another set of tandem sigmatropic rearrangements, leading to vinyl imidate formation. Collectively, this work showcases the rich array of chemistry one can discover using these ynamides.

N-allyl-N-sulfonyl ynamides as synthetic precursors to amidines and vinylogous amidines. An unexpected N-to-C 1,3-sulfonyl shift in nitrile synthesis.

Asymmetric aza-[3+3] annulation in the synthesis of indolizidines: an unexpected reversal of regiochemistry.

Treatment of pyrrolidines of type (I) with enals in the presence of the chiral ammonium salt allows a diastereo- and enantioselective access to indolizidines via an unprecedented head—to—tail annulation.

Asymmetric Aza-[3 + 3] Annulation in the Synthesis of Indolizidines: An Unexpected Reversal of Regiochemistry.

The Pd-catalyzed or thermally-induced treatment of ynamides of type (I) with amines allows convenient access to amidines.

Huifang Dai

Papers

N-allyl-N-sulfonyl ynamides as synthetic precursors to amidines and vinylogous amidines. An unexpected N-to-C 1,3-sulfonyl shift in nitrile synthesis.

Asymmetric aza-[3+3] annulation in the synthesis of indolizidines: an unexpected reversal of regiochemistry.

Asymmetric Aza-[3 + 3] Annulation in the Synthesis of Indolizidines: An Unexpected Reversal of Regiochemistry.

N-Allyl-N-sulfonyl Ynamides as Synthetic Precursors to Amidines and Vinylogous Amidines. An Unexpected N-to-C 1,3-Sulfonyl Shift in Nitrile Synthesis.